Assessment of oral methotrexate intolerance in Japanese adult patients with rheumatoid arthritis.

AIM: The objective of this study was to assess the gastrointestinal side (GI) effects of oral methotrexate (MTX) in Japanese adult patients with rheumatoid arthritis (RA). METHODS: In this single-center retrospective study, 112 Japanese adult patients (over 18 years old) with RA were examined by Methotrexate Intolerance and Severity assessment in Adults (MISA) questionnaire. RESULTS: Forty-five (40.2%) of patients were MTX intolerant (MISA score ≥1). Twelve patients (11.2%) were moderate-to-severe MTX intolerant (MISA cross-product score ≥4). The most common GI side effects of MTX were gastric discomfort (26.8%), followed by loss of appetite or dysgeusia (14.3%), fatigue and lethargy (12.5%), and nausea (10.7%). CONCLUSIONS: Japanese adult patients with RA showed a high prevalence of MTX intolerance even in low-dose oral MTX. The MISA questionnaire was practical for finding patients with MTX intolerance.

Predicting therapeutic response in IgG4-related disease based on cluster analysis.

To bring the clinical practice of immunoglobulin (Ig)G4-related disease (IgG4-RD) close to personalized medicine, we classified the patient groups and clarified the therapeutic responses of each group. A total of 147 patients enrolled in our registry were classified into four groups by cluster analysis with the software. The therapeutic responses and prognosis of each group were examined. The cluster analysis classified the subjects into four groups: Cluster 1, patients who presented with prominent hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia; Cluster 2, patients who presented with eosinophilia, elevated concentrations of serum IgG, IgG4, and IgE, and in whom CRP tended to be positive; Cluster 3, patients with younger onset and serum levels of IgG, IgG4, and IgE and peripheral eosinophil counts lower than the other clusters; and Cluster 4, patients with elder onset and low peripheral eosinophil counts. The amounts of glucocorticoid for maintenance treatment were from 5 to 7 mg/d in all groups, but the amounts were significantly greater in Cluster 1 (patients with hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia) than in Cluster 4 (elder onset patients, relatively low concentrations of peripheral eosinophils). With regard to the use of immunosuppressants and the relapse rate, there were high frequencies in Cluster 1 and Cluster 3 (younger onset patients who presented with mild elevations of serum IgG and IgG4). On the other hand, Cluster 4 showed a low rate of relapse and often could discontinue steroids. The present results suggest that personalized medicine could be provided in IgG4-RD by classifying patients based on their clinical features.

Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder Presenting as Primary Bone Lymphoma in a Patient with Rheumatoid Arthritis.

Primary bone lymphoma (PBL) is a rare disorder. We herein present a case of other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) presenting as PBL. A 63-year-old woman was diagnosed with rheumatoid arthritis and had been treated with methotrexate for seven years. Two months before admission, she suffered from pain in the limbs. Magnetic resonance imaging revealed multiple irregular lesions in the bones of the limbs, which showed an uptake of (18)F-FDG on positron emission tomography. A biopsy of the right radius revealed diffuse large B-cell lymphoma, leading to the diagnosis of OIIA-LPD. She received rituximab-containing regimens resulting in a complete response.

[A case of pseudoscleroderma as paraneoplastic syndrome due to carcinoma of cervical uteri].

A 65-year-old female began experiencing arthralgia, morning stiffness and psychroesthesia in April 2000. She visited a rheumatologist and was suspected of having early-stage rheumatoid arthritis. She was referred to our hospital, and was admitted in December 2000. At that time, sclerosis of the skin was advanced, and Raynaud's phenomenon was confirmed. The patient also exhibited nailfold bleeding, and was diagnosed as having systemic scleroderma. She visited a gynecologist for screening and cervical uteri carcinoma was confirmed. She underwent surgery in March 2001, and subsequently, sclerosis in her skin was almost stopped. We believe that these clinical symptoms were related to paraneoplastic syndrome. We therefore immunochemically investigated the pathogenesis of paraneoplastic syndrome and found that connective tissue growth factor (CTGF) might be involved and transforming growth factor-beta (TGF-beta) might not be involved in this case.

[Superficial esophageal carcinoma successfully treated with combined chemotherapy and radiotherapy].

A 47-year-old man was admitted to our hospital with the chief complaint of epigastralgia. Endoscopic examination revealed a 0-IIa + IIc lesion in the middle thoracic esophagus, and a biopsy specimen was diagnosed as squamous cell carcinoma. The depth of the cancerous invasion was judged to be sm by endoscopic ultrasonography, and no metastasis to other organs or lymph nodes was detected. Although we believed curative resection was possible, we performed combined chemotherapy and radiotherapy because the patient refused surgery. After 2 courses of chemoradiotherapy, the cancer had disappeared clinically. We have found no evidence of recurrence for 1 year and 8 months. For the patient with superficial esophageal carcinoma who has a high risk or refuses surgery, chemoradiotherapy may be a reasonable alternative.